Predictive value of microRNA-132 and its target gene NAG-1 in evaluating therapeutic efficacy of non-steroidal anti-inflammatory drugs treatment in patients with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a common chronic rheumatic disorder, accompanied by the differential expression of various microRNAs (miRNAs) in patients suffering from the condition, some of which have the potential to serve as novel complementary AS biomarkers. During this study, AS patients were recruited in connection with our investigation into the correlation of microRNA-132 (miR-132) in peripheral blood and its target gene NAG-1 expressions in relation with the clinical efficacy of non-steroidal anti-inflammatory drugs (NSAIDs) treatment in patients with AS. A total of 218 AS patients who had been previously treated with oral diclofenac sodium and were placed into either the response (n = 175) or non-response groups (n = 43) following a 16-week period of therapeutic evaluation. An additional 113 healthy patients were also recruited for the purposes of the study. AS patient peripheral blood samples were obtained at the 0th, 8th, and 16th week, with the corresponding samples of the healthy patients collected at week 0. The expressions of miR-132 and NAG-1 were detected by RT-qPCR and analyzed using a ROC curve for the elucidation of the diagnostic value of peripheral blood miR-132 expressions as well as their predictive value among AS patients undergoing NSAIDs treatment. The targeting relations of miR-132 and NAG-1 were validated by microRNA.org and luciferase assay. Greater levels of peripheral blood miR-132 expression were observed among AS patients prior to treatment, in comparison to the healthy patients in the study. Prior to treatment, the area under the miR-132 ROC curve (AUC) of AS patients was 0.965, with a critical point of 2.605. The sensitivity and specificity of miR-132 were 91.7 and 97.3%, respectively, in regard to the AS diagnostic clinical efficacy. In comparison with the non-response group, the miR-132 expression of patients in the response group exhibited descended levels while the mRNA expression of NAG-1 increased. The ROC results indicated that the AUC of miR-132 was 0.876 with its sensitivity and specificity observed to be 95.3 and 80.0%, respectively. The AUC of NAG-1 was 0.912 with its sensitivity and specificity observed to be 76.6 and 79.1%, respectively. In comparison with the high miR-132 expression group and the low NAG-1 mRNA expression group, significantly improved blood biochemistry indexes, sign indexes, blood indexes, and adverse reaction rate were observed among the low miR-132 expression group and the high NAG-1 mRNA expression group. The microRNA.org and luciferase assay revealed NAG-1 to be a target of miR-132. Based on the results of this study, it was concluded that the expressions of MiR-132 and NAG-1 could serve as biological markers in the prediction of the therapeutic efficiency of NSAID treatment in AS patients.

Silencing Prx1 and/or Prx5 sensitizes human esophageal cancer cells to ionizing radiation and increases apoptosis via intracellular ROS accumulation.

AIM: To investigate whether down-regulation of peroxiredoxin 1 (Prx1) and/or peroxiredoxin 5 (Prx5) sensitizes human esophageal cancer cells to ionizing radiation (IR). METHODS: Human esophageal carcinoma cell lines Eca-109 and TE-1 were used. Prx mRNA expression profiles in Eca-109 and TE-1 cells were determined using RT-PCR. Two highly expressed isoforms of Prxs, Prx1 and Prx5, were silenced by RNA interference (RNAi). Following IR, intracellular reactive oxygen species (ROS) and apoptosis were measured using flow cytometry, the activities of catalase, superoxide dismutase and glutathione peroxidase were measured, and the radiosensitizing effect of RNAi was observed. Tumor xenograft model was also used to examine the radiosensitizing effect of RNAi in vivo. RESULTS: Down-regulation of Prx1 and/or Prx5 by RNAi does not alter the activities of catalase, superoxide dismutase and glutathione peroxidase, but made human tumor cells more sensitive to IR-induced apoptosis both in vitro and in vivo. When the two isoforms were decreased simultaneously, intracellular ROS and apoptosis significantly increased after IR. CONCLUSION: Silencing Prx1 and/or Prx5 by RNAi sensitizes human Eca-109 and TE-1 cells to IR, and the intracellular ROS accumulation may contribute to the radiosensitizing effect of the RNAi.

Platelet glycoprotein IIb/IIIa (HPA-1 and HPA-3) polymorphisms in patients with hemorrhagic fever with renal syndrome.

This study investigated the relationship between human platelet alloantigen (HPA) polymorphisms of glycoprotein IIb/IIIa and hemorrhagic fever with renal syndrome (HFRS). HPA-1 and HPA-3 genotyping was performed with allele-specific primer polymerase chain reaction in 104 patients with HFRS and 100 normal individuals as controls. The relationships between gene polymorphisms of HPAs and HFRS and the disease severity were analyzed. The results indicated no significant difference in HPA-1 genotype distributions (p > 0.05), but a significant difference in the distributions of genotype and allele frequencies of HPA-3 between HFRS patients and controls (p < 0.01). The distributions of HPA-3 genotype and allele frequencies differed significantly between patients with different clinical types and the HPA-3 b allele was more frequently observed in patients with more severe clinical types. These results indicate that HPA-3 polymorphism may be one of the inherited risk factors associated with the susceptibility of hantavirus infection and the disease severity of HFRS.

Serum thrombospondin-1 is altered in patients with hemorrhagic fever with renal syndrome.

Hemorrhagic fever with renal syndrome (HFRS) is a severe acute viral disease with pathological changes of impaired capillary and small vessels and thrombocytopenia. In this study, serum thrombospondin (TSP)-1 concentration in patients with HFRS was determined to explore its possible role in the pathogenesis of HFRS. The concentration of TSP-1 was measured using a competitive enzyme-linked immunoabsorbent assay. Significantly decreased levels of serum TSP-1 were observed in HFRS patients at febrile and hypotensive phases compared with those in the controls. The serum levels of TSP-1 in HFRS patients with more severe clinical types was reduced more profoundly than those in patients with milder clinical types at febrile and hypotensive phases, although the differences in TSP-1 were not significant. It was indicated that insufficient production or increased consumption of TSP-1, or both of these, may contribute to the impairment of capillary and small vessels and the development of hypotension at the early stage of HFRS, and the decreased degree may be associated with disease severity.

Intensity of platelet beta(3) integrin in patients with hemorrhagic fever with renal syndrome and its correlation with disease severity.

beta(3) Integrin has been identified as a cellular receptor for Hantaan virus, which causes hemorrhagic fever with renal syndrome (HFRS). To investigate the relationship between intensity of the platelet membrane beta(3) integrin (CD61) and disease severity, the percentage of CD61-positive platelets and the mean fluorescence intensities (MFI) of platelet CD61 were determined in patients with HFRS by flow cytometry. The intensity levels of CD61 in patients with HFRS were significantly higher than those in the controls and correlated with the clinical phases of the disease. The CD61 intensity at the oliguric phase was inversely correlated with platelet count and serum albumin, and positively correlated with white blood cell count, blood urea nitrogen, serum creatinine, and alanine aminotransferase levels. The results suggest that the intensity levels of platelet CD61 were elevated and associated with clinical phases and disease severity in patients with HFRS, and the intensity of platelet beta(3) integrin in patients with HFRS may be indicative of disease severity.